In general, the invention relates to methods and kits for the treatment and diagnosis of systemic anthrax infection.
Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. The bacterium sporulates upon contact with air and is subsequently resistant to degradation by heat, radiation, desiccation, and disinfectants. Anthrax most commonly infects wild and domestic lower vertebrates, but can infect humans (e.g., cutaneously, through inhalation, or through ingestion) when exposed to infected animals or contaminated animal products. Mortality arises from complications related to vascular injury, including increased systemic permeability, microthromboses, and shock. Hemoconcentration from the loss of water in the blood is a major manifestation of systemic anthrax, as is hemorrhagic mediastinitis.
Angiopoietins (e.g., Ang-1 and Ang-2) are secreted proteins produced by cells in the vasculature. Ang-1 is made by vascular smooth muscle. Ang-1 expression results in endothelial cell survival against injurious stimuli, the reduction of inflammatory protein expression on the surface of endothelial cells, and the maintenance of tight connections between endothelial cells to prevent vascular permeability. Conversely, Ang-2 is made by endothelial cells and antagonizes the effects of Ang-1, thus promoting inflammation. Preliminary studies have shown circulating Ang-2 rises rapidly upon systemic anthrax infection, suggesting that the level of Ang-2 in serum provides an early indicator of severe disease.
There exists a need in the art for a simple, efficient, and minimally invasive diagnostic test to identify systemic anthrax infection in a subject. In addition, effective treatments of systemic anthrax infection are needed for those diagnosed with the disease.